A critical property of the blood-brain barrier (BBB) is the unique complex of tight junctions (TJs) that exist between adjacent endothelial cells, which impede paracellular diffusion and help maintain brain homeostasis. Numerous lines of evidence implicate BBB TJ dysfunction as a primary contributor to central nervous system (CNS) disease. While it has become increasingly evident that pro-inflammatory high-fat Western diets contribute to CNS disease, the impact of such diets on the BBB TJs has not been fully elucidated. Likewise, the potential benefit of omega-3 (?3) polyunsaturated fatty acids (PUFAs) on BBB TJ regulation also remains unclear. The goal of this examination is to elucidate the effects of dietary fats on BBB TJ integrity and protein regulation, respective to inflammatory contributions. This study is divided into two aims: 1) Determine the effect of Western vs. omega-3 based diets on BBB TJ integrity and protein regulation over time. Evaluations of BBB TJ protein regulation (microvascular isolate) and paracellular integrity (permeability marker) corresponding with high and low fat diets, both with and without primary ?-3 PUFAs (EPA and DHA), will be assessed over 14- and 28-weeks of dietary treatment (C57BL/6 mice). Supportive evaluations will assess primary dietary variables, inflammatory components, and PPAR? alterations. 2) Determine the effect of Western vs. omega-3 based diets on BBB TJ integrity and protein regulation against an acute inflammatory challenge. Herein, 14-week dietary treatments will be run against an acute inflammatory challenge via lipopolysaccharide (LPS), followed by evaluation sets identified in aim-1. Assessing BBB TJs at key inflammatory time-points, post-LPS injection, will allow for the delineation of BBB TJ susceptibility and resilience respective to dietary treatments. This exploratory study will provide novel insight into the impact of dietary fas on the health and resilience of the BBB TJs, as well as a greater understanding of inflammatory influences. Additionally, it will serve as the foundation for future examinations respective to BBB regulation and disease outcomes. The aims of this study address priorities of National Institutes of Health, respective to the National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA), National Center for Complementary and Alternative Medicine (NCCAM), and the Office of Dietary Supplements (ODS).